This invention relates to the fields of organic synthesis, organoboron chemistry, combinatorial chemistry and medicinal chemistry.
Heterocyclic derivatives containing one or more nitrogen atoms are exceedingly common in a large variety of pharmaceuticals and pharmaceutical intermediates. Such systems are often essential for the overall utility of molecules of this type, including their use as active pharmaceutical ingredients for the treatment of some of the most common diseases, including cancer, cardiovascular diseases, CNS diseases, etc.
Among the most widely known examples of heterocycles are several types of benzodiazepine derivatives which are widely used as pharmaceuticals. For several decades the benzodiazepine ring system has been one of the most effective scaffolds for the development of therapeutic agents. Among the various substitution patterns, most common are those present in such widely used anxiolytic agents as diazepam (Thompson, L. A; Ellman, J. A., Chem. Rev., 1996, 96, 555), while less common are the structures present in various peptidomimetics (Evans, B. E.; et al., J. Med. Chem., 1987, 30, 1229. Bhalay, G.; et al., Tet. Lett., 1997, 38, 8375).
A large variety of nitrogen heterocycles occur widely in nature and many variants of these have found applications as active pharmaceutical ingredients. For example, azasugars, such as polyhydroxylated piperidine, indolizine and quinolizidine alkaloids have attacted considerable interest in recent years because they exhibit potent glycosidase inhibitory activity, resulting in a wide range of pharmacological properties against cancer, HIV and other diseases (Stütz, A. E. Iminosugars as Glycosidase Inhibitors, Nojirimycin and beyond, Wiley-VCH, 1999). Several natural or synthetic azasugars have found applications as therapeutic agents, as a result of their behavior as glucosidase inhibitors and other bioactivities. For example n-butyl deoxynojirimycin and N-nonyl-deoxy-galactonojirimycin were shown to have potent antiviral activity against several viruses, including HIV and hepatitis B virus (D. Durantel, et al. J. Virology, (2001), p. 8987; A. Mehta, et al, Ant. Agents and Chemoherapy, 4004 (2002)).